ApoE-/-Fas-/- C57BL/6 mice:: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia
ApoE-/-Fas-/- C57BL/6 mice:: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia
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DOI：
10.1194/jlr.m600512-jlr200
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发表时间：
2007-04-01
影响因子：
6.5
通讯作者：
Tsao, Betty P.
中科院分区：
文献类型：
--
作者：
Feng, Xuebing;Li, Hongyun;Tsao, Betty P.
为了建立狼疮性动脉粥样硬化的小鼠模型，我们建立了载脂蛋白E缺陷(apoE(-/-))和Fas(LPR/LPR)(Fas(-/-))C57BL/6小鼠。在正常饮食中，5月龄apoE(-/-)Fas(-/-)小鼠的肾小球绒毛面积增大，严重的蛋白尿，循环自身抗体水平增加，肾脏和血管病变中的凋亡细胞增加。此外，与apoE(-/-)Fas(+/+)小鼠相比，双基因敲除小鼠的动脉粥样硬化病变增加，但血清总胆固醇和非高密度脂蛋白胆固醇水平降低。此外，雌性apoE(-/-)Fas(-/-)小鼠的椎骨骨密度(BMD)和骨体积密度(BV/Tv)低于年龄匹配的雌性apoE-/-Fas(+/+)小鼠。与apoE(-/-)Fas(+/+)和apoE(+/+)Fas(-/-)小鼠相比，apoE(-/-)Fas(-/-)小鼠的载脂蛋白颗粒apoB-100上的循环氧化磷脂(OxPL)含量降低，血清OxPL抗体水平升高，且与主动脉病变面积(r=0.58)、肾小球绒毛面积(r=0.87)、BMD(r=-0.57)和BV/TV(r=-0.72)显著相关。提示apoE(-/-)Fas(-/-)小鼠模型可用于狼疮动脉粥样硬化和骨量减少的研究。Ig G抗OxPL与狼疮样疾病、动脉粥样硬化和骨丢失的相关性表明，这些疾病过程有一个共同的途径。
To establish a mouse model of accelerated atherosclerosis in lupus, we generated apolipoprotein E-deficient (apoE(-/-)) and Fas(lpr/lpr) (Fas(-/-)) C57BL/6 mice. On a normal chow diet, 5 month old apoE(-/-)Fas(-/-) mice had enlarged glomerular tuft areas, severe proteinuria, increased circulating autoantibody levels, and increased apoptotic cells in renal and vascular lesions compared with either single knockout mice. Also, double knockout mice developed increased atherosclerotic lesions but decreased serum levels of total and non-HDL cholesterol compared with apoE(-/-)Fas(+/+) littermates. Moreover, female apoE(-/-)Fas(-/-) mice had lower vertebral bone mineral density (BMD) and bone volume density (BV/TV) than age-matched female apoE-/-Fas(+/+) mice. Compared with apoE(-/-) Fas(+/+) and apoE(+/+)Fas(-/-) mice, apoE(-/-)Fas(-/-) mice had decreased circulating oxidized phospholipid (OxPL) content on apoB-100 containing lipoprotein particles and increased serum IgG antibodies to OxPL, which were significantly correlated with aortic lesion areas (r = 0.58), glomerular tuft areas (r = 0.87), BMD (r = -0.57), and BV/TV (r = -0.72). These results suggest that the apoE(-/-) Fas(-/-) mouse model might be used to study atherosclerosis and osteopenia in lupus. Correlations of IgG anti-OxPL with lupus-like disease, atherosclerosis, and bone loss suggested a shared pathway of these disease processes.